This proposal will examine the relationships between the antiviral (AV) and cell growth inhibitory (CGI) effects of interferon (IFN). Towards this we will employ two clones of Swiss mouse 3T3 cells, one of which is sensitive to the AV and CGI effects of IFN (AV+CGI+) while the other (isolated and characterized by us recently) is sensitive to the AV but resistant to the CGI effects (AV+CGI-). We will determine the types of polypeptides induced by IFN in both cell types by analysing electrophoretically the in vivo synthesized cellular proteins or proteins synthesized in a cell-free translational system on one and/or two dimensional polyacrylamide gels. This should enable us to determine the putative IFN-induced proteins mediating the CGI effects. We will map the proteins synthesized in quiescent AV+CGI+ and AV+CGI- 3T3 cells stimulated to proliferate by the additions of platelt derived growth factor (PDGF) and epidermal growth factors (EGF) in the presence or absence of IFN to establish the basis of IFN's inhibitory effect on initiation of cellular DNA synthesis. Using cell fusion techniques we will determine the role of cytoplasmic factors in specifying the CGI and AV effects of IFN. The effect of IFN on two pre-replicative events (protein methylation and induction of poly (ADP-R) synthetase) initiated by mitogens in quiescent cells will be ascertained. The use of the two clones of 3T3 cells in this respect will enable us to determine whether the observed inhibitory effects of IFN on the two pre-replicative events are relevant to the inhibition of DNA synthesis. Analysis of IFN's AV and CGI effects are important, not only in understanding the regulatory events in viral replication and cellular proliferation, but also because IFN has proven to be an effective agent in the treatment of a variety of viral infections and cancer in humans. Undoubtedly knowledge on the basis of IFN's action will play a key role in designing specific antiviral and antitumor agents in the future.